Biomedical Engineering – From Theory to Applications

Trends in Interdisciplinary Studies Revealing
Porphyrinic Compounds Multivalency Towards Biomedical Application
cases, light exposure leads to a relocalization of the sensitizers (Moan & Berg, 1992; Moan &
Peng, 2003; Spikes, 1989).
Singlet oxygen is a highly reactive ROS that interacts with proteins, nucleic acids and lipids.
Singlet oxygen has a short lifetime within the cell and can migrate in tissues less than 20 nm
after its formation. Therefore, the induced injury by singlet oxygen action is highly
localized. Nevertheless, generation of about 9 x 10 8 molecules of singlet oxygen per tumor
cell significantly reduces the cell surviving fraction (Dysart et al., 2005).
PDT leads to a molecular interplay between cell death pathways, balancing between
apoptosis, necrosis and autophagy (Dewaele et al., 2010). Generally, photosensitizers which
specifically target mitochondria induce ROS-mediated cell death by apoptosis (Oleinick et
al., 2002), while autophagy occurs during PDT protocols involving sensitizers that localize
to the endoplasmic reticulum (ER) (Buytaert, 2006; Kessel, 2006). Nonetheless, Pavani et al.
(2009) demonstrated that photodynamic efficiency is directly proportional to membrane
binding and is not totally related to mitochondrial accumulation. The presence of zinc in the
photosensitizer decreases mitochondrial binding and increases membrane interactions,
leading to improved PDT efficiency.
Recent evidence points out that mitochondria and ER associated with B-cell lymphoma 2 are
among the cellular targets damaged in PDT protocols, impacting both apoptosis and
autophagy. Autophagy may function as a prosurvival or a death pathway in PDT. The
former function is obvious at low-dose PDT conditions, whereas the latter one contributes to
the killing of cells exhibiting a phenotype that precludes the development of an apoptotic
response, or of those cells that surviving to the initial wave of apoptosis after high-dose PDT
(Kessel 2007; Pattingree, 2005). Apoptosis dominates as a mechanism of cell death in those
cells having a fully competent apoptotic machinery, whereas autophagy seems to be
responsible for cell death when apoptosis is compromised (Xue et al., 2007).
ROS are biologically multifaceted molecules, despite their simple chemical structure.
Depending on the magnitude and profile of ROS generation in biological systems, on
cellular location and on the redox balance, ROS can elicit cell death or cell proliferation. On
one hand, aerobic organisms adapted themselves to the injurious oxidative attack and even
learned how to use ROS in their own favor, as signaling molecules. On the other hand, ROS
proved to be powerful weapons in fighting against infection or as therapeutic armentarium
exploiting oxidative stress. Radiotherapy is one of the clearest examples of anti-cancer
treatment, whose mechanism relies primarily on ROS, combining the properties of an
extremely efficient DNA-damaging agent with high spatial focusing on tumor.
Radiotherapy limitation derives mainly from the carcinogenic potential of the ionizing
radiation and from the deleterious side-effect associated with the inflammatory response
triggered by necrosis. Radiation memory underlies long-lasting effects of radiotherapy in
tumors, but also contributes to persistent damage and dysfunctions of bystander normal
cells. Taking also advantage of ROS cytotoxic potential, but with significantly less sideeffects
than radiotherapy, PDT is a fascinating example of biomedical engineering,
combining and targeting towards diseased tisssues a photosensitizer, light and oxygen. It is
an interdisciplinary approach involving chemistry, physics, biology and medicine for
synergizing and fine-tuning all the three above mentioned components towards an efficient
and highly targeted treatment regimen.
Although other classes of molecules have been tested and used as photosensitizers,
porphyrins and porphyrin-like structures are undoubtly the most relevant for biomedical
applications. Porphyrins and porphyrin-like structures have long been of interest for PDT
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